This proposal seeks to determine the toxicological significance of carbon disulfide (CS2)-induced tyrosine hydroxylase (TH) activation. Attempts will also be made to determine the nature of this activation. To this end inhalation experiments will be made in which the exposure duration and dose of CS2 delivered in the inspired air will be varied. Simultaneous measurements of TH activity, and catecholamine concentrations will be carried out in brain, striatal tissue, heart and adrenal. Determinations of striatal TH activity in CS2-treated and control rats will also be carried out in situ. The results from these experiments will be correlated with striatal dopamine turnover studies. Investigations of CS2-induced changes in the affinity of the cofactor 6MPH4 for TH will also be conducted. Since dopamine-beta-hydroxylase (DBH) has been shown to be induced by the catecholamine depleting agent reserpine, studies of DBH activity in the adrenal during the time course of CS2 exposure will be made. During the course of the experiments which demonstrate TH activation TH activation by CS2 it was found that air gassed chamber controls showed decreased brain TH activity after only four hours. This surprising "deactivation" of TH will be examined in the above experiments.